Abstract: Injurious falls are common, morbid, and costly for nursing home (NH) residents, particularly those with Alzheimer?s Disease and Related Disorders (ADRD). Medications may be the most common, modifiable risk factor for injury, yet no studies have comprehensively compared the risks and benefits of drugs used to manage cardiovascular disease in the NH. Our long-term goal is to prevent injurious falls in NH residents. This proposal will identify cardiometabolic drugs with a poor net clinical benefit in ADRD and other NH residents. Further, we will identify subsets of NH residents who are at greatest risk for injurious falls while taking these drugs in an effort to target deprescribing. The following specific aims are proposed: 1) determine which cardiometabolic drugs are associated with an increased risk of injurious falls in NH residents; 2) determine which cardiometabolic drugs have poor net clinical benefit, defined as a decrease in ?home time?; and 3) develop and validate a model to predict the imminent and long-term absolute risk of injurious falls in NH residents. We will then determine whether the effects of cardiometabolic drugs on injurious fall risk differs in resident subgroups including residents with a high predicted risk of injury and ADRD residents. The central hypothesis is that it is possible to identify risky patterns of cardiometabolic drug use in ADRD and other NH residents. We will leverage an existing database that has linked claims data from Medicare Parts A and B with pharmacy data (Medicare Part D), clinical characteristics (Minimum Data Set), and facility level characteristics (OSCAR). Using this database we will conduct a retrospective analysis on all long-stay U.S. NH residents enrolled in a Medicare fee-for-service plan between the years 2013-2018 (~850,000 residents and >80,000 injurious falls). This research is innovative because few studies have evaluated the safety and efficacy of cardiometabolic drugs in NH residents. In Aim 1, we will compare injurious fall rates in new users of antihypertensive, antihyperglycemic, and anticoagulant drugs, with new users of a comparator drug within the same class. Propensity scores and a number of advanced causal inference techniques will be used to address polytherapy and potential bias. A similar approach will be used in Aim 2. Results from Aims 1 & 2 will allow for a clinically meaningful discussion of risks and benefits when deprescribing medications in NH residents. Specific Aim 3 will validate a model to identify NH residents at greatest risk for injury, and identify subgroups who are the most vulnerable to injurious falls when using cardiometabolic drugs, including ADRD residents. The research team has experience with predicting falls and fractures and knowledge of geriatrics, pharmacoepidemiology, and Medicare data necessary to complete this project. Our findings will inform a standardized approach to reduce imminent and long-term injurious falls risk in the NH through screening and deprescribing efforts. Knowledge gained from this proposal could ultimately result in a decrease in injurious falls in NH residents, with a subsequent reduction in morbidity and healthcare costs.